PhD Student, Hudson Institute of Research
Can we use cells from the placenta to help preterm babies breathe on their own?
Bronchopulmonary dysplasia (BPD) is a chronic lung disease that represents the principal cause of morbidity in infants born before 28 weeks of gestation. Survivors of BPD suffer higher-than-normal rates of chronic respiratory illness and adverse neurological outcomes, including cerebral palsy. There is no therapy for BPD. In the US, the incidence of BPD in preterm infants has been consistently increasing since 1993.
BPD is defined as the requirement for respiratory support at 28 days of life. Although respiratory support is life saving, it results in chronic inflammation and injury of the lungs. Thus, BPD arises from ventilator-induced lung inflammation and injury in preterm infants.
Human AECs (hAECs) show promise in lung inflammation associated with the development of BPD. Human AECs are easily obtained from the placenta, which is usually discarded at birth. Preclinically, hAECs reduce lung inflammation and prevent lung injury in animals subject to infection or ventilation.
Long-term mechanical ventilation of preterm lambs causes lung inflammation and injury consistent with the pathology of BPD. The only preclinical intensive care research unit (PICRU) in the southern hemisphere was recently established for long-term care of preterm lambs, which allows us to manage lambs for a period of weeks, in a way that mimics human neonatal care.
We are now in a unique position to perform definitive preclinical studies required to demonstrate efficacy of postnatal hAECs to prevent or treat BPD, and to inform design of future randomised controlled trials.
Abstract: With a view to developing a cell therapy for chronic lung disease, human amnion epithelial cells (hAECs) have been shown to prevent acute lung injury. Whether they can repair established lung disease is unknown. We aimed to assess whether hAECs can repair existing lung damage induced in mice by bleomycin and whether the timing of cell administration influences reparative efficacy. In addition, we aimed to characterize the effect of hAECs on fibroblast proliferation and activation, investigating possible mechanisms of reparative action. hAECs were administered intraperitoneally (IP) either 7 or 14 days after bleomycin exposure. Lungs were assessed 7 days after hAEC administration. Bleomycin significantly reduced body weight and induced pulmonary inflammation and fibrosis at 14 and 21 days. Delivery of hAECs 7 days after bleomycin had no effect on lung injury, whereas delivery of hAECs 14 days after bleomycin normalized lung tissue density, collagen content, and α-SMA production, in association with a reduction in pulmonary leucocytes and lung expression of TGF-β, PDGF-α, and PDGF-β. In vitro, hAECs reduced proliferation and activation of primary mouse lung fibroblasts. Our findings suggest that the timing of hAEC administration in the course of lung disease may impact on the ability of hAECs to repair lung injury.
Pub.: 10 Oct '12, Pinned: 28 Aug '17